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Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Cancers Originate from Somatic Mutations in a Single Cell02:21

Cancers Originate from Somatic Mutations in a Single Cell

Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Cancer02:18

Cancer

Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

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Comparative Lesions Analysis Through a Targeted Sequencing Approach
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Comparative Lesions Analysis Through a Targeted Sequencing Approach

Published on: November 5, 2019

ヒトのがんにおける様々な体的変異パターンと経路の変化.

Zhengyan Kan1, Bijay S Jaiswal, Jeremy Stinson

  • 1Department of Molecular Biology, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, USA.

Nature
|July 30, 2010
PubMed
まとめ

この研究では,441の癌腫瘍の1,507の遺伝子で2,576の体内変異が特定されました. GNASとMAP2K4を含む重要な変異遺伝子は,新しいがん治療薬の潜在的標的を提供している.

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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors

Published on: September 20, 2016

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Last Updated: Jun 10, 2026

Comparative Lesions Analysis Through a Targeted Sequencing Approach
08:16

Comparative Lesions Analysis Through a Targeted Sequencing Approach

Published on: November 5, 2019

Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing
11:02

Detecting Somatic Genetic Alterations in Tumor Specimens by Exon Capture and Massively Parallel Sequencing

Published on: October 18, 2013

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
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科学分野:

  • ゲノミクスゲノミクスとは
  • 癌生物学 癌生物学について
  • 分子腫瘍学 分子腫瘍学

背景:

  • ガンゲノムの体内変異は,疾患のメカニズムを理解する上で極めて重要です.
  • 標的型療法を開発するには,包括的なゲノム特性分析が必要です.

研究 の 目的:

  • 主要なヒトがんタイプにおける体性変異を体系的に特定し,特徴づけること.
  • ガン治療の新薬標的を発見する.

主な方法:

  • 441種類の腫瘍 (乳腺,肺,卵巣,前立腺) の全ゲノムシーケンシング.
  • ソマティック変異とコピー番号の変化の識別と統計分析.
  • 重要な変異遺伝子の機能研究 (GNAO1,MAP2K4).

主要な成果:

  • 1,507のコード遺伝子の2,576の体内変異を特定しました.
  • 腫瘍タイプ/サブタイプにおける突然変異率と遺伝子組の有意な変化が発見されました.
  • 77の著しく変異した遺伝子 (GRM8,BAI3,AGTRL1,LPHN3など) と35の追加変異遺伝子 (GNASなど) が発見されました.
  • 腫瘍生成における変異GNAO1とMAP2K4の機能的役割が実証されている.

結論:

  • 人間の癌の突然変異は多様で,サブタイプに特異的です.
  • Gタンパク質結合受容体やシグナル伝達経路の成分を含む多数の潜在的な治療標的を特定しました.
  • ガン発症におけるG-アルファサブユニットの役割の拡大を強調する.